This study was designed to elucidate the effects of meluadrine tartrate on maternal metabolic responses and fetal hemodynamics in unanesthetized, chronically instrumented pregnant goats. After the administration of meluadrine tartrate to pregnant goats or directly to fetuses, changes in heart rate (HR), arterial blood pressure and arterial blood pH, gasses, electrolytes and metabolic responses were measured. The constant administration of meluadrine tartrate (0.1 microg. kg(-)(1). min(-)(1)) to pregnant goats resulted in the increases of maternal HR, glucose and free fatty acid and the decrease of maternal blood K(+) concentration. The direct escalating administration of meluadrine tartrate (0.01, 0.03 and 0.1 microg. kg(-)(1). min(-)(1)) did not increase the fetal HR, while ritodrine hydrochloride (0.3, 1 and 3 microg. kg(-)(1). min(-)(1)) to fetuses increased the fetal HR dose-dependently. The present study suggests that meluadrine tartrate has a mild influence relative to the effects of ritodrine to the maternal metabolic responses and fetal cardiovascular function.

01 Jan 2002·Japanese Journal of Pharmacology

Effects of Meluadrine Tartrate and Ritodrine Hydrochloride on Oxytocin-Induced Uterine Contraction, Uterine Arterial Blood Flow and Maternal Cardiovascular Function in Pregnant Goats

Article

Author: Tsuyomu Ikenoue ; Yoshio Matsuda ; Satoshi Kouno ; Hiroshi Sakamoto

This study was designed to elucidate the effects of meluadrine tartrate on oxytocin-induced uterine contraction and maternal hemodynamics in unanesthetized, chronically instrumented pregnant goats. After the administration of meluadrine tartrate or ritodrine hydrochloride to pregnant goats, changes in heart rate (HR), arterial blood pressure (AOP), and arterial blood pH and gasses (P(O2) and P(CO2)) in the mother, as well as changes in intrauterine pressure (IUP) and uterine arterial blood flow (UBF), were measured. The escalating administration of meluadrine tartrate (0.03, 0.1, 0.3 and 1 micro g. kg(-)(1). min(-)(1)) or ritodrine hydrochloride (1, 3, 10 and 30 microg. kg(-)(1). min(-)(1)) to the maternal femoral vein caused a marked and similar inhibition in oxytocin-induced uterine contraction (a rise in IUP). By these escalating dosings, maternal HR was increased dose-dependently in both treatment groups; however, the degree of the HR increase in the meluadrine tartrate-treatment group was significantly less than that in the ritodrine hydrochloride-treatment group. Furthermore, the degree of the UBF decrease in the meluadrine tartrate-treatment group was significantly less than that in the ritodrine hydrochloride-treatment group. The present study suggests that meluadrine tartrate has a mild influence on the maternal cardiovascular function relative to the effects of ritodrine taking the potent efficacy on oxytocin-induced uterine contraction into account.

01 Jan 2001·Chemical and Pharmaceutical BulletinQ4 · MEDICINE

Racemization Kinetics of Meluadrine Tartrate in Aqueous Solution.

Q4 · MEDICINE

Article

Author: YAMAMOTO, Youichi ; NAGATA, Osamu ; MATSUO, Kazuya ; TSUJI, Akira ; YAMAZAKI, Masahiro ; KADO, Noriyuki ; KATO, Hideo

The kinetics of racemization of meluadrine tartrate in aqueous solution was investigated by HPLC, over the pH range of 1.2 to 12 at 40, 60 and 80 degrees C. The racemization was followed by measuring both the residual (R)-enantiomer and formed (S)-enantiomer of meluadrine. The pH-racemization rate profile of meluadrine showed a minimum racemization rate constant between pH 4 and 6, and the rate constant increased rapidly with decreasing pH below pH 3. In the basic region, the racemization rate constant showed a maximum at around pH 9. Four pathways of racemization of meluadrine are proposed, depending on the dissociation state of the phenolic and amino groups. The calculated racemization rate-pH profile agreed well with the observations. The values of activation energy (95-115 kJ/mol) suggest that a similar quinoid intermediate is involved throughout the pH range examined. The objective of this study is to clarify the racemization mechanism of benzylalcohol derivative with phenoric group. This study offers fundamental knowledge for the other benzylalcohol derivatives, which have similar moiety structure.

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Indication	Highest Phase	Country/Location	Organization	Date
Obstetric Labor, Premature	NDA/BLA	-	Mitsubishi Tanabe Pharma Corp.	-
Obstetric Labor, Premature	NDA/BLA	JP	-	-
Obstetric Labor, Premature	NDA/BLA	-	Abbott Laboratories	-

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